Nucleophilic addition/cycloaddition

The allenes 1 directly connected with an electron-withdrawing substituent have been used successfully as synthetic building blocks for more than four decades (see Scheme 7.1). The polarization of the C=C double bonds by the acceptor substituent allows a wide and very useful range of subsequent reactions, for example nucleophilic additions, cycloadditions and miscellaneous syntheses of heterocydes. 

Cyclobutanes can be conveniently prepared from cyclobutene derivatives through electrophilic addition, catalytic hydrogenation, nucleophilic addition, cycloaddition as well as light-induced addition reactions. 

The reactions of sulfenes are many and various and their presentation requires that they be sorted out into categories which, hopefully, help to show a measure of order in this abundance. We have chosen three main groups nucleophilic additions, cycloadditions, and thermal and photochemical processes. This arrangement is somewhat arbitrary, since the reactions are not all well-understood and, of those that are, not all fit perfectly into the chosen scheme. It is our view that this ordering, however imperfect, does serve the purpose of providing the reader with both an overview of sulfene chemistry and a means of gaining access to a specific piece of information. 

Addition reactions, electron transfer reactions, and reactions involving the opening of the fullerene cage (chemical surgery) have been thoroughly studied on fullerenes. Other reactions such as nucleophilic additions, cycloaddition reactions, free-radical additions, halogenations, hydroxylation, redox reactions, and metal transition complexations have been reported for Cgo as well. Furthermore, fullerenes are easily reduced by electron-rich chemical reagents as well as electrochemically. Their oxidation, however, is considerably more difficult to achieve [17]. Thus, electrochemical measurements showed the formation from the monoanion to the hexaanion [18]. 

SCHEME 18.27. Sequential Wolff rearrangement/nucleophilic addition/cycloaddition. 

Nitrile A-oxides, under reaction conditions used for the synthesis of isoxazoles, display four types of reactivity 1,3-cycloaddition 1,3-addition nucleophilic addition and dimerization. The first can give isoxazolines and isoxazoles directly. The second involves the nucleophilic addition of substrates to nitrile A-oxides and can give isoxazolines and isoxazoles indirectly. The third is the nucleophilic addition of undesirable nucleophiles to nitrile A-oxides and can be minimized or even eliminated by the proper selection of substrates and reaction conditions. The fourth is an undesirable side reaction which can often be avoided by generating the nitrile A-oxide in situ and by keeping its concentration low and by using a reactive acceptor (70E1169). 

In addition there are certain other methods for the preparation such compounds. Upon heating of the thionocarbonate 2 with a trivalent phosphorus compound e.g. trimethyl phosphite, a -elimination reaction takes place to yield the olefin 3. A nucleophilic addition of the phosphorus to sulfur leads to the zwitterionic species 6, which is likely to react to the phosphorus ylide 7 via cyclization and subsequent desulfurization. An alternative pathway for the formation of 7 via a 2-carbena-l,3-dioxolane 8 has been formulated. From the ylide 7 the olefin 3 is formed stereospecifically by a concerted 1,3-dipolar cycloreversion (see 1,3-dipolar cycloaddition), together with the unstable phosphorus compound 9, which decomposes into carbon dioxide and R3P. The latter is finally obtained as R3PS ... 

Therefore, the preference of the cycloadditions is opposite in direction to the biases observed in nucleophilic additions of 2-substituted 9,10-dihydro-9,10-ethanoanthracen-11-ones (34) (dibenzobicyclo[2.2.2]octadienones) and in electrophilic additions of 2-substituted 9,10-dihydro-9,10-ethenoanthracenes (dibenzobicyclo[2.2.2]octatrienes) 71 [103]. 

Perhaps the most characteristic property of the carbon-carbon double bond is its ability readily to undergo addition reactions with a wide range of reagent types. It will be useful to consider addition reactions in terms of several categories (a) electrophilic additions (b) nucleophilic additions (c) radical additions (d) carbene additions (e) Diels-Alder cycloadditions and (f) 1,3-dipolar additions. 

The cycloaddition between a nitrilimine 319 and an aroyl substituted heterocyclic ketene aminal 318 has been found to be stepwise, involving an initial nucleophilic addition of 318 to 319 followed by intramolecular cyclocondensation of the intermediate 320 providing fully substituted pyrazole 321 (Eq. 36) [92]. When Ar was the 2,4-dinitrophenyl group, the intermediate 320 was isolable and required forcing conditions (xylene, reflux, 10 h) to undergo cyclization ... 

Several other types of addition reactions of alkenes are also of importance and these are discussed elsewhere. Nucleophilic additions to electrophilic alkenes are covered in Section 2.6 and cycloadditions involving concerted mechanisms are encountered in Sections 6.1 to 6.3. Free radical addition reaction are considered in Chapter 11. 

A series of 3-substituted-2-isoxazoles are prepared by the following simple procedure in situ conversion of nitroalkane to the silyl nitronate is followed by 1,3-dipolar cycloaddition to produce the adduct, which undergoes thermal elimination during distillation to furnish the isoxazole (Eq. 8.74). 5 Isoxazoles are useful synthetic intermediates (discussed in the chapter on nitrile oxides Section 8.2.2). Furthermore, the nucleophilic addition to the C=N bond leads to new heterocyclic systems. For example, the addition of diallyl zinc to 5-aryl-4,5-dihydroi-soxazole occurs with high diastereoselectivity (Eq. 8.75).126 Numerous synthetic applications of 1,3-dipolar cycloaddition of nitronates are summarized in work by Torssell and coworker.63a... 

Jug and co-workers investigated the mechanism of cycloaddition reactions of indolizines to give substituted cycl[3,2,2]azines <1998JPO201>. Intermediates in this reaction are not isolated, giving evidence for a concerted [8+2] cycloaddition, which was consistent with results of previous theoretical calculations <1984CHEC(4)443>. Calculations were performed for a number of substituted ethenes <1998JPO201>. For methyl acrylate, acrylonitrile, and ethene, the concerted [8+2] mechanism seems favored. However, from both ab initio and semi-empirical calculations of transition states they concluded that reaction with nitroethene proceeded via a two-step intermolecular electrophilic addition/cyclization route, and dimethylaminoethene via an unprecedented two-step nucleophilic addition/cyclization mechanism (Equation 1). 

Imino-1,2,4-thiadiazoles such as 27 react with electron-deficient alkynes to afford arylimino thiazoles such as 28. There has been some speculation as to the mechanism of this reaction, which may involve a 1,3-dipolar cycloaddition or a stepwise nucleophilic addition (Equation 6) <1996CHEC-II(4)307>. 

Reactions of stable mesito- and duronitrile oxides with 1-chloroalkyl isocyanates R R2CC1NC0 (R1 = CF3, R2 = Ph, 4-MeC6H4 R1 = CC13, R2 = H) gave oxadiazolones 176. The double adducts are formed by the cycloaddition of one nitrile oxide molecule at the isocyanate C=N bond and the nucleophilic addition of the chloroalkyl moiety to a second nitrile oxide molecule (344). 

I.4.2.2. Cross-linldng of Polymers Among applications of nitrile oxides, cross-linking of polymers is of main importance. Both nucleophilic addition and 1,3-dipolar cycloaddition are the pertinent reactions. 

Apart from some special cases, the ring-closure step in the course of the synthetic pathway is often condensation reaction and, thus, these transformations can be considered as cyclocondensations . Reactions following a few other mechanisms like cycloaddition, electrocyclization, and intramolecular nucleophilic addition of electron pair of an atom to a multiple bond also occur relatively often. Because of the fairly large complexity of the ring systems belonging to this chapter, the treatment according to the heteroatomic combinations seemed the most straightforward. Thus, the fused... 

Ring opening reaction of alkylidenecyclopropanone acetals readily proceeds in the presence of Lewis or Bransted acids to produce l-alkylidene-2-oxyallyl cation, which is provided for the reaction with nucleophiles such as chloride, alcohols, siloxyalkenes, and furans. The reaction of this cation with the carbon nucleophiles gives products of [4 + 3] and [3 + 2] cycloaddition as well as those of nucleophilic addition. The modes of addition reactions are controlled by the oxy group of the cation and by the reaction conditions including solvent. 

We have recently developed a novel method for the generation of alkylideneallyl cations from alkylidenecyclopropanone acetals (8, 9). This method provides a nice opportunity to examine the selectivity of reactions of the ambident cation with various nucleophiles including siloxyalkenes (10) and furans (11). The reaction of the cation with the carbon nucleophiles gives [4 + 3] and [3 + 2] cycloaddition products as well as simple nucleophilic addition products. These results are summarized in this chapter. 

The observed preferential electrophilic attack on carbon D of C70 under Friedel-Crafts conditions (CHC13/A1C13) is consistent with the large HOMO coefficient of this carbon (Figure 13). This is in contrast to the fact that nucleophilic addition (7,35-38) and cycloaddition (38-40) to C70 favor carbons A and B, which are most pyramidalized and have large LUMO coefficients (Figure 13). 

Nucleophilic additions to (cyclohexadienone)Fe(CO)3 complexes (218) occur in a dia-stereospecific fashion (Scheme 56)197. For example, the Reformatsky reaction of ketone (218a) affords a simple diasteromeric alcohol product19715. The reduction of (1-carbo-methoxycyclohexa-l,3-dien-5-one)Fe(CO)3 (218b) to give 219 has been utilized in the enantioselective synthesis of methyl shikimate. In a similar fashion, cycloadditions of (2-methoxy-5-methylenecyclohexa-l,3-diene)Fe(CO)3 (220) occur in a diastereospecific fashion198. 

Several different methods of sidewall functionalisation, such as fluorination, radical addition, nucleophilic addition, electrophilic addition and cycloaddition, have been developed (Tasis et al., 2006). The sidewalls of vertically aligned CNTs have been functionalised with DNA using azide units as photoactive components. The azi-dothymidine reacted photochemically with sidewalls of CNTs utilising [2+1] cycloaddition. The oligonucleotides were grown in situ on the sidewalls of CNTs and the DNA-modified CNTs were obtained after the deprotection of the nucleic acid (Moghaddam et al., 2004). 

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